In mammalian early embryos, the transition from maternal to embryonic control of gene expression requires timely degradation of a subset of maternal mRNAs (MRD). Recently, zygotic genome activation (ZGA)-dependent MRD has been characterized in mouse 2-cell embryo. However, in early embryos, the dynamics of MRD is still poorly understood, and the maternal factor-mediated MRD before and along with ZGA has not been investigated. Argonaute 2 (Ago2) is highly expressed in mouse oocyte and early embryos. In this study, we showed that Ago2-dependent degradation involving RNA interference (RNAi) and RNA activation (RNAa) pathways contributes to the decay of over half of the maternal mRNAs in mouse early embryos. We demonstrated that AGO2 guided by endogenous small interfering RNAs (endosiRNAs), generated from double-stranded RNAs (dsRNAs) formed by maternal mRNAs with their complementary long noncoding RNAs (CMR-lncRNAs), could target maternal mRNAs and cooperate with P-bodies to promote MRD. In addition, we also showed that AGO2 may interact with small activating RNAs (saRNAs) to activate Yap1 and Tead4, triggering ZGA-dependent MRD. Thus, Ago2-dependent degradation is required for timely elimination of subgroups of maternal mRNAs and facilitates the transition between developmental states.

在哺乳动物早期胚胎中，从母体控制到胚胎控制的基因表达过渡需要适时降解母体mRNA（MRD）的一部分。最近，合子基因组激活（ZGA）依赖的MRD已在小鼠2细胞胚胎中得到了表征。然而，在早期胚胎中，人们对MRD的动力学仍然知之甚少，并且尚未研究ZGA之前以及与ZGA一起由母体因子介导的MRD。Argonaute 2（Ago2）在小鼠卵母细胞和早期胚胎中高度表达。在这项研究中，我们证明了Ago2依赖的降解涉及RNA干扰（RNAi）和RNA激活（RNAa）途径，导致小鼠早期胚胎中超过一半的母体mRNA衰减。我们证明，由内源性小干扰RNA（endosiRNAs）引导的AGO2可以由母体mRNA及其互补的长非编码RNA（CMR-lncRNAs）形成的双链RNA（dsRNA）产生，可以靶向母体mRNA并与P体协同作用促进MRD。此外，我们还表明AGO2可能与小的激活RNA（saRNA）相互作用以激活Yap1和Tead4，从而触发ZGA依赖性MRD。因此，需要Ago2依赖性降解来及时消除母体mRNA的亚组，并促进发育状态之间的过渡。